Homeobox-containing genes of the Hox class have been implicated in patterning and specification during embryonic development and in the development and function of specific tissues and structures. We have performed preliminary in situ hybridization experiments that demonstrate the expression of the endogenous Hoxa4 gene in the skin of fetal and newborn mice, notably in hair follicles. We wish to pursue these various preliminary observations with the following series of pilot project aims: 1) we will examine the temporal, spatial, and cellular distribution of expression of Hoxa4 in the murine skin, with particular emphasis on hair follicles, during embryonic and post-natal development and in adult animals; 2) will initiate studies to identify regions of the Hoxa4 gene that regulate its expression in the skin using transgenic approaches; and 3) we will investigate the possible modulation of Hoxa4 expression by retinoic acid. This will be accomplished by treatment of in vitro cultures of dissected hair follicles with retinoic acid and monitoring of gene expression of the endogenous gene expression by in situ hybridization. The goal of these pilot studies will be to provide evidence for the hypothesis that Hoxa4 is involved in hair follicle development and function and to begin to elucidate how this gene is regulated during this process. As Hox genes have been implicated in both proliferative and differentiative events, understanding their function in normal skin will be important for elucidating their potential role in skin disorders and diseases.